Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined.
Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS.
The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25–0.74; 0.0068).
Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.
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Study concept and design: K.A.R. Acquisition of data: K.A.R., S.Y., D.A., E.S., M.M.W. Analysis and interpretation of data: K.A.R., M.M.W., D.A., E.S. Manuscript preparation: M.M.W., D.A., K.A.R., Critical revision of the manuscript: P.J.O., S.D., K.N., G.L.B., K.A.R. Statistical analysis: M.M.W., K.A.R.
The authors declare no competing interests.
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The institutional review board at the University of Pennsylvania approved this study. Informed consent was waived. This study was conducted in accordance with the Declaration of Helsinki.
This work was funded by a grant from the Basser Young Leadership Council of the Basser Center for BRCA (KAR) and by an Anonymous Foundation (KAR).
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Wattenberg, M.M., Asch, D., Yu, S. et al. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer (2019). https://doi.org/10.1038/s41416-019-0582-7